Article Figures & Data

Figures

A, Whole-brain voxel-based morphometry between marijuana users and control participants. Images are thresholded at z = 2.5. The most significant increases in gray matter density were in the left nucleus accumbens extending to the hypothalamus, sublenticular extended amygdala, and amygdala (Tables 2 and 3). B, Associations between gray matter density and drug use measures; p < 0.0125 was considered to be significant after correcting for 4 comparisons (Table 4). GMd, Gray matter density. C, Nucleus accumbens volume was increased in marijuana users and was associated with drug use measures. Error bars represent SE. An asterisk above the bar chart on left indicates that significance met p < 0.05 uncorrected (p = 0.037; Table 2), which was a trend effect after correcting multiple comparisons. The association with drug use, after correcting for 4 comparisons (p = 0.05/4, or 0.0125), was determined to be a trend toward significance (Table 4). CON, Controls; MJ, marijuana participants.

Shape analysis. 2D results of the shape analysis of the amygdala (A) and the nucleus accumbens (B) show areas that are significantly different between marijuana and control participants (left); 3D results are shown on right. Below each colorized statistical map, differences in shape were significantly associated with several drug use measures. An asterisk after the p-value in A and after the left/right color legend in B indicates a significant correlation (corrected). Please see Table 4 for significance after correcting for multiple comparisons. C, Color maps indicate bivariate correlations between modalities in the left nucleus accumbens (left). The relationship between gray matter density and shape and between gray matter density and volume differed between marijuana usersr and control participants; one asterisk indicates a trend correlation; two asterisks indicate a significant correlation (corrected). Please see Table 6 for significance after correcting for multiple comparisons. GMd, Gray matter density; Vol, volume.

Coordinates are in MNI space and are listed in millimeters. Reported p values are uncorrected; please see Materials and Methods for whole-brain correction. Gray matter density (GMd) measures reflect ROI average density. Volume is indicated in cubic millimeters. Shape values were obtained by identifying the voxel showing the peak differences between groups within each ROI and extracting the value of that peak voxel in each individual subject. The mean difference between relative group averages is shown in millimeters. For measures, group differences between the 20 controls and 20 MJs are reported as t statistics. Individual subject values were covaried in a general linear model (GLM) to account for age, sex, alcohol use, and cigarette smoking, yielding F and adjusted p values. Values at p < 0.05 uncorrected are shown in bold; an asterisk indicates that these values met correction for multiple comparisons (e.g., p < 0.0125).

All clusters were derived from a VBM analysis. Significant clusters consisted of at 40 mm3 (5 voxels) thresholded at z = 3.3 (p < 0.001), with a peak voxel of z > 3.5 (p < 0.0005). Coordinates are in MNI space and are listed in millimeters.

Values of gray matter density (GMd), volume, and shape were entered into linear regressions with the four measures of marijuana use, yielding the reported r2 and p-values. p < 0.05 uncorrected are in bold; an asterisk indicates that these values met correction for multiple comparisons across four regions (e.g., p < 0.0125).

Total brain is composed of gray matter + white matter + intraventricular CSF. All volumes are reported in cubic millimeters. All structures were entered into a univariate general linear model to examine how ICV, sex, and group (MJ or CON) affected variance of volumes of structures.

p < 0.05 uncorrected are bolded. Please note, after correcting for multiple comparisons (p < 0.002), that only the left accumbens correlation between volume and gray matter density (GMd) and the left amygdala correlations between volume and shape were significant in controls.

I read with great interest the report by Gilman et al. (2014)
examining the effects of recreational marijuana use by young adults. The
authors concluded that brain regions implicated in reward and drug
addiction behavior, i.e., the nucleus accumbens and amygdala "...revealed
greater density values in marijuana users than in control participants."
After comparing MRI brain scans of casual users to those of controls,
rese...

I read with great interest the report by Gilman et al. (2014)
examining the effects of recreational marijuana use by young adults. The
authors concluded that brain regions implicated in reward and drug
addiction behavior, i.e., the nucleus accumbens and amygdala "...revealed
greater density values in marijuana users than in control participants."
After comparing MRI brain scans of casual users to those of controls,
researchers speculated that regional differences were abnormalities caused
by cannabis use that attribute to drug addiction. While this is an
intriguing interpretation, I feel at least two points deserve further
discussion.

First, there were no measures of cognitive performance or any other
behaviors in the current report. This makes it nearly impossible to
interpret the meaning of any brain measure differences. As Di Domenico and
Eaton (1988) pointed out in their classic paper, "Without a quantifiable
concept of behavior we run the risk of performing neurophysiological
experiments that have no behavioral correlates but which entice us to make
unwarranted speculations without the neural basis of behavior." As a
result, causal explanations regarding drug addiction cannot be determined
by these differences in complex anatomical brain structures.

Second, the marijuana group reported use of multiple other
substances, making it impossible to disentangle the effects of marijuana
from those of other drugs. Without inclusion of a marijuana-only group or
a group that reported use of multiple other drugs except marijuana, it
seems premature to conclude that "...marijuana exposure, even in young
recreational users, is associated with exposure-dependent alterations of
the neural matrix of core reward structures..." Moreover, it is unclear
whether these regional differences predate cannabis use or are a result of
poly-drug use.

Given the above concerns, measuring regional brain differences offers
no basis for speculation about arbitrary drug addiction behavior between
cannabis users and controls. Structural brain differences between men and
women exist, however this does not prove that they differ in ability based
on gender. Without overt quantifiable behavioral measures and controlling
for poly-drug use, these anatomical differences should not be attributed
to marijuana use primarily.

Conflict of Interest:

I read with great interest this article correlating neuroanatomical
changes in casual cannabis users versus non-users. However, the
authors repeatedly and explicitly state a causative relationship between
the cannabis use and the anatomic changes throughout the article, only to
state in the second-to-last paragraph that no causative relationship can
be concluded due to the cross-sectional design of this study. Even mor...

I read with great interest this article correlating neuroanatomical
changes in casual cannabis users versus non-users. However, the
authors repeatedly and explicitly state a causative relationship between
the cannabis use and the anatomic changes throughout the article, only to
state in the second-to-last paragraph that no causative relationship can
be concluded due to the cross-sectional design of this study. Even more,
the press release from the Society for Neuroscience [1] and the narrative
in news stories resulting from this manuscript [2,3] do not explicitly
state this very obvious caveat. While the correlative relationship
reported here is statistically strong, a longitudinal study design is
necessary to make the causative claims throughout the first 29 paragraphs
and abstract of this manuscript. Again, this very critical distinction in
study design is not noted until the end of the manuscript. A plausible
alternative interpretation of this data is that the neuroanatomical
abnormalities predate the drug use and make the individuals more likely to
use cannabis. By reversing the causative relationship here, we would
suppose that greater anatomical changes would cause increased consumption.
With that said, there is abundant evidence showing an empirical link
between tetrahydrocannabinol administration and neuroanatomical changes in
rodents. However, the repeated claims of a causative relationship in this
manuscript and related press articles are not warranted based solely on
the results reported here.

References

[1]. Society for Neuroscience Press Release. "BRAIN CHANGES ARE
ASSOCIATED WITH CASUAL MARIJUANA USE IN YOUNG ADULTS". Accessed April
16th, 2014 at http://www.sfn.org/Press-Room/News-Release-
Archives/2014/Brain-Changes-Are-Associated-with-Casual-Marijuana-Use-in-
Young-Adults